Intestine Flashcards
What is the lifecycle of an enterocyte?
- mature enterocytes are tall & columnar w/ luminal microvilli which contain a surface glycocalyx that houses the digestive & absorptive enzymes
- the mature cells do not proliferate
- enterocytes move up the crypt & intestinal villus to the extrusion zone at the villus tip, where effete enterocytes are discarded into the fecal mass by apoptosis
- turnover rate for enterocytes is rapid
- in 3-week-old pigs turnover rate is 2-3 days
What are the epithelial cells of the intestine?
- enterocytes
- undifferentiated or crypt epithelial cells
- goblet cells
- paneth cells
- enteroendocrine cells
- M cells
what do undifferentiated or crypt epithelial cells do?
- they have no digestive capacity
- they are the progenitor cells that replace all other epithelial cell types
What do goblet cells do?
- secrete mucus
- their numbers tend to increase aborally throughout the length of the intestine
What do paneth cells do?
- located near the crypt base (present in primates, horses, rodents, & possibly swine)
- unlike all the other cells of the intestinal surface, these cells migrate toward the crypts rather than the villus tips
- they produce bactericidal substances (cryptdin & lysins) which protect proliferating crypt cells from infection
What do enteroendocrine cells do?
- in the crypts produce & secrete into surrounding tissue (not into intestinal lumen) serotonin, gastrin, cholecystokinin, etc. which coordinate function (secretion, peristalsis, & digestion) of GIT
What do M cells do?
cover the gut associated lymphoid tissue (GALT) & serve important functions in the uptake of antigens from the intestinal lumen
What does lymphoid tissue do in the intestines?
- the intestinal lymphoid tissue represents 25% of the total body’s lymphoid mass in most animals
- normal gut does not response to normal food antigens, in spite of the fact that the average person ingests ~70,000 kg of antigens in a lifetime
How does postmortem autolysis of the intestinal mucosa affect necropsy of the intestines?
- rapidly results in loss of superficial intestinal villar epithelium which interferes w/ histological detection of certain important pathogens (ex: cryptosporidia, E. coli) & diagnosis of villar atrophy (both v important for diagnostics of neonatal D+)
- hence, for diagnostics of neonatal D+, it is highly recommended to perform necropsy on an animal that just died (or was just euth’d)
- swine practitioners often submit live piglets w/ D+ to diagnostic lab (if at all possible), which will be euth’d immediately before necropsy to avoid autolytic changes in intestines
How to necropsy intestines?
- strive to obtain formalin fixed intestinal samples as soon as possible & then proceed w/ the standard necropsy exam
- standard exam: varies according to sp
- important to systemically examine in situ the external surface & position of the entire GIT (dx adhesions, torsions, displacements, etc.) & then examine mucosa & contents of each portion of GIT w/ associated LNs & mesentery
- sample collection for microbiology (refrigerated or frozen) & pathology (formalin fixed) should be collected from each portion of GIT
- common error is placing too much tissue in too little formalin - “rule of thumb” is 10:1 formalin to tissue ratio
What are developmental anomalies of the intestines?
- atresia
- megacolon
What is atresia?
congenital absence of a normal opening or normal patent lumen (ex: atresia ani, atresia coli, etc.)
What is megacolon?
- a large distended colon filled w/ feces
what is congenital megacolon?
- inappropriate innervation (lack of myenteric plexuses) in pigs, dogs, cats, overo foals, & humans
- atresia ani can also result in megacolon
What is acquired megacolon?
- secondary to damage to the colonic innervation; occasionally happens in Car hit by a car
What is ileus?
- hypomotility resulting in a functional obstruction of the bowel
- there are no gross lesions other than atonic dilation of the intestine
- it occurs in all spp
What are the causes of ileus?
- post-surgical due to bowel manipulation at surgery
- peritonitis from any cause
- severe abdominal pain
- electrolyte imbalances (esp. hypokalemia)
What are some causes of mechanical intestinal obstruction?
- enteroliths occasionally in Eq
-trycho- & phytobezoars in rumen - feed impaction
- cecal impaction
- sand colic
- linear foreign bodies
- intestinal stricture
- intussusception
- rectal prolapse secondary to tenesmus or excessive postpartum straining
- intestinal volvulus, torsion, & strangulation
Which spp does feed impaction occur in?
All of them
Who does cecal impaction occur in and why?
- old horses b/c of high roughage diet or poor dentition
Who does sand colic occur in and why?
- large amounts of ingested sand can accumulate anywhere in the equine colon, resulting in impaction
Who do linear foreign bodies occur most commonly in?
carnivores
What are intestinal strictures the result of?
healing w/ scarring & fibrosis:
- post-enterotomy healing -> fibrosis -> stricture
- rectal stricture
Pathogenesis of rectal strictures?
- recurrent rectal prolapse can result in circumferential necrosis & subsequent fibrosis -> stricture
- salmonellosis in pigs -> thrombosis of the cranial hemorrhoidal artery (lack of collateral circulation) -> necrosis -> circumferential fibrosis -> stricture
What is intussusception?
- when one segment of intestine becomes telescoped into the immediately distal segment of intestine
What are the clinical features of intussusception?
- similar to those of intestinal obstruction & venous infarction (in more severe cases)
- red to black discolouration depends on the degree of vascular compromise, ranging from congestion & edema to hemorrhage & necrosis
What is the intussusceptum?
the trapped segment
What is the intussuscipiens?
the enveloping portion of the intestine
What is the cause of intussusception?
generally unknown but is thought to be associated w/ intestinal irritability & hypermotility due to enteritis or intestinal parasites
What can spontaneously happen w/ intussusceptions?
- can spontaneously reduce by sloughing of the infarcted mucosa, which is passed in the feces
- the site of sloughing is repaired by granulation tissue (due to loss of scaffold) resulting in a circumferential fibrosis/scar & intestinal stricture
How can you tell antemortem from postmortem intussusceptions?
- b/c peristalsis continues after death, intestinal invaginations can occur postmortem
- POSTMORTEM (OR TERMINAL) INVAGINATIONS ARE EASILY REDUCED, THERE IS NO VASCULAR COMPROMISE (EDEMA, CONGESTION, HEMORRHAGE), NO ADHESIONS (PERITONEAL SURFACES ARE SMOOTH & GLISTENING), & NO NECROSIS
What is rectal prolapse a type of?
intussusception
What is volvulus ?
twisting of the intestine on its mesenteric axis
What is torsion?
rotation of the abomasum, colon, or cecum along its long axis
What is intestinal strangulation ?
- occurs in Eq w/ pedunculated lipomas which wrap around the intestinal mesentery or the bowel, causing ischemia, colic, & death
- pedunculated lipomas may rotate about their pedicle cutting off their own blood supply
- when this occur, they undergo necrosis & mineralization
What are internal hernias?
- displacements of intestine through a normal or pathologic foramen in the abdominal cavity
- most common of these occur in horses & include herniation through mesenteric tears & the epiploic foramen
what are external hernias?
- formed when a hernial sac, formed by a pouch of parietal peritoneum, penetrates outside the abdominal cavity
- types of external herniation include umbilical, diaphragmatic, hiatal, inguinal, scrotal, & perineal
In which types of hernias does intestinal incarceration occur?
both internal & external
What happens when volvulus, torsion, strangulation, intussusception, or incarceration results in the compression of a the mesenteric vesseles?
-> resulting in ischemic necrosis (infarction)
- venous infarction is a result of occlusion of the thin-walled mesenteric veins
- b/c the arterial supply is anatomically more resistant to occlusion, blood is pumped into the twisted segment but cannot drain
- TRANSMURAL CONGESTION, EDEMA, HEMORRHAGE, & EVENTUAL NECROSIS (VENOUS INFARCTION) WILL RESULT
what happens at surgery or necropsy w/ intestinal venous infarction?
- the twisted segment of intestine is distended w/ gas & hemorrhagic fluid & is discoloured dark red to black
- there is a SHARP LINE OF DEMARCATION btwn the affected & normal intestine
- during surgery, it is v important to determine the viability of the bowel after reduction of the volvulus
- the affected/ dead segment of intestine remains dark red & thickened after reduction of the volvulus b/c of severe congestion & edema that progressed to hemorrhage & necrosis (venous infarction)
- Intestinal stasis & toxemia &/or bacteremia & septicemia may result from bacterial overgrowth & anoxic bowel necrosis
- toxemia & intestinal rupture may result in death
- if reduction of a volvulus results in re-established circulation, reperfusion injury may also occur (mediated by oxygen free radicals, complement activation, & inflammation)
What is iatrogenic rectal tearing?
- may occur secondary to rectal palpation
- presence of blood on a rectal sleeve after palpation is cause for concern b/c peritonitis may be the result of penetration to the peritoneal cavity
What is “brown gut” (ceroidosis)?
- rare condition caused by the accumulation of a brown ceroid pigment (formerly called lipofuscin) in the lysosomes of smooth muscle cells of the tunica muscularis
- it does not cause any clinical signs but may be an indicator of a metabolic or nutritional disorder (vitamin E deficiency or high concentration of polyunsaturated fatty acids in the diet)
What is muscular hypertrophy of the distal ileum?
- an idiopathic segmental & circumferential thickening of the ileal tunica muscularis most commonly found in horses & pigs
- in both species, it is often an asymptomatic lesion
What is hemomelasma ilei?
- another unique lesion in the horse
- these are red, brown to black plaques on the ileal & jejunal subserosa
- they are various stages of hemorrhage caused by larval migrations of strongyles (Strongylus edentatus)
- they have no clinical significance
however, they may provide a hint of an inadequate deworming program
What is the pathogenesis of cranial mesenteric arteritis & thrombosis?
- Strongylus vulgaris causes mesenteric arteritis & thrombosis in Eq
- ingested larvae penetrate the large intestinal wall & migrate on or w/in the tunica intima (histo: tunica intima consists of endothelium, subendothelial CT, & an internal elastic mb) along the intestinal arterioles & arteries towards the cranial mesenteric root
- larval migration causes vascular damage, inflammation, (verminous arteritis), thrombosis, intimal fibroplasia, & aneurysms
- occasionally detached thromboemboli occlude downstream smaller intestinal arteries & cause local ischemia resulting in intermittent colic episodes, even though fatal incidents are rare most likely due to extensive collateral circulation
- effective anthelmintics markedly reduced the prevalence of S. vulgaris infection in Eq
What is lymphangiectasia?
(lacteal dilation)
- most common protein-losing enteropathy in Ca
What are the clinical signs of lymphangiectasia?
- D+, steatorrhea, hypoproteinemia -> ascites
What are the causes of lymphangiectasia?
- acquired secondary to lymph vessel obstruction caused by granulomatous or neoplastic diseases
- sometimes, it is a part of chronic inflammatory bowel disease
- congenital developmental disorder of the lymphatic vessels
what is diarrhea?
abnormally frequent discharge of semisolid of fluid fecal matter
What are the most important clinical consequences of D+?
DEHYDRATION & subsequent ACIDOSIS
How can D+ lead to hypovolemic shock?
D+ -> dehydration -> hypovolemia -> hemoconcentration -> inadequate tissue perfusion & oxygen concentration -> inefficient energy generation in tissues by anaerobic glycolysis -> hypoglycemia leads to ketoacidosis -> acidosis is enhanced by fecal bicarbonate loss & by inadequate renal excretion of H+ ions & inadequate absorption of bicarbonate due to inadequate renal perfusion -> systemic increase in intracellular hydrogen ion concentration & a decrease in intracellular potassium ion concentration -> decrease in neuromuscular control of myocardial contraction -> further decrease in tissue perfusion -> vicious cycle culminates in hypovolemic shock
How do you diagnose D+ on postmortem?
- sunken eyes in orbits
- subcutis is tacky
- skin lacks elasticity (in fresh animals)
- in piglets, urates precipitation may be present in the renal medulla
What is D+ with normal intestines?
- intestinal morphology is not affected but the animal has D+
What are the different types of normal intestine D+?
secretory & osmotic
What is the pathogenesis and etiology of secretory diarrhea?
- enterotoxigenic E. coli (ETEC) infection in neonatal pigs, calves, lambs, & humans causes secretory D+
- these bacteria are able to colonize the small intestinal enterocytes by way of their pilus antigens (fimbria), which anchor them to the enterocytes
- thus these bacteria are not flushed out by peristalsis
- the bacteria produce toxins that cause enterocytes to secrete water & electrolytes
- the net result is D+
- B/c the enterocytes are not damaged, NO LESIONS ARE OBSERVED, & absorption is functional
- CHYLE IS PRESENT IN THE MESENTERIC LYMPHATIC VESSELS similar to animals w/o enteric disease, indicating that unlike the malabsorptive diseases of the small intestine, absorption proceeds normally in cases of enterotoxic colibacillosis
What is the pathogenesis and etiology of osmotic diarrhea?
- ruminal acidosis results in higher osmolarity of the gastrointestinal contents
What is the pathogenesis of malabsorptive diarrhea?
- caused by a decreased absorptive surface usually a consequence of damage to absorptive enterocytes, to microvilli on the surface of enterocytes, &/or to undifferentiated crypt cells
- this is usually manifested as villous atrophy
- the loss of the absorptive-digestive villous enterocytes causes maldigestion & malabsorption
- furthermore, b/c ingesta & normal alimentary secretions are unabsorbed, they are degraded further & fermented in the intestine by bacteria, increasing the osmolarity of the intestinal contents, w/ a subsequent increase in the fluid content of the bowel
What occurs w/ damage to mature absorptive enterocytes w/ malabsorptive D+?
- destruction of these cells results in loss of enterocytes & villous atrophy
- b/c the regenerative crypt cells are not attacked by pathogens w/ a tropism for villous enterocytes, disease w/ villous enterocyte damage are not necessarily fatal
- the lost cells are replaced by the maturing cells migrating along the basement membrane from the crypt to the villous
- the naked basement membrane stimulates contraction of the villi resulting in villous atrophy
- the contraction may be a function of the smooth muscle in the lamina propria
- the functionally immature migrating crypt cells cover the villi
- often, these immature cells becomes squamoid (flat) in an effort to cover the maximum areas of basement mb
- however, if ‘naked’ basement membranes of the adjacent villi contact each other, they will adhere, resulting not only in villous blunting but also in villous fusion, preventing the reformation/regeneration of normal villi
What is the etiology of malabsorptive D+ with damage to mature absorptive enterocytes?
rotavirus, coronavirus, Cryptosporidium parvum
What occurs w/ damage to undifferentiated crypt cells w/ malabsorptive D+?
- loss of the undifferentiated epithelial cells in the base of the crypts means loss of the cells capable of rapid mitosis, & thus regeneration of the epithelium is impaired.
- this type of loss is more severe & often fatal, compared w/ just the loss of villous enterocytes
What is the etiology of malabsorptive D+ with damage to undifferentiated crypt cells?
- parvovirus, BVD virus, rinderpest virus, & some mycotoxins
What is the etiology of ulcerative enterocolitis?
Salmonella, Brachyspira, Lawsonia, bovine coccidiosis, Clostridium spp.
What is the etiology of ulcerative enterocolitis?
- microorganism cause extensive necrosis of superficial epithelium, lamina propria, &/or blood vessels
- result is massive & acute necrohemorrhagic or fibrinonecrotic enteritis
- absorptive surface is lost (malabsorption) & ulceration allows for loss of interstitial & plasma fluids
What are other disorders (other than ulcerative colitis) of the intestinal mucosa that result in the loss of proteins due to increased intestinal permeability?
Johne’s disease, lymphangiectasia, lymphoma, etc.
what are some non-intestinal causes of D+?
- pancreatic insufficiency, pancreatitis, R-heart failure, ruminal acidosis, etc.
What are common etiologies for infectious undifferentiated diarrhea in piglets younger than 3 wks?
rotavirus, coronavirus, ETEC, Isospora suis*
- = may cause mortality
What are common etiologies for infectious undifferentiated diarrhea in calves younger than 3 wks?
rotavirus, coronavirus, ETEC, & cryptosporidium
What are etiologies for infectious undifferentiated diarrhea in lambs younger than 3 wks?
rotavirus (less common), coronavirus (rare), ETEC (less common), Cryptosporidium (rare)
What are etiologies for infectious undifferentiated diarrhea in foals younger than 3 wks?
rotavirus (less common), coronavirus (rare), Cryptosporidium (rare)
Which undifferentiated diarrhea causative agent in animals younger than 3 wks is zoonotic?
cryptosporidium
What is undifferentiated neonatal D+?
- this disease complex has SIMILAR clinical & gross pathological presentation despite being caused by different pathogens in neonates of various spp
What are the clinical signs in all spp of undifferentiated neonatal D+?
- variable degree of dehydration
- weakness & potentially inappetence
- if D+ is prolonged, weight loss
- perineum stained w/ diarrheic feces
- yellow pasty to watery diarrhea
- usually high morbidity & variable mortality (depending on etiology)
- no differentiating gross lesions
What is seen on necropsy in all spp w/ undifferentiated neonatal D+?
nonspecific findings
- usually marked dehydration
- distended small intestines w/ watery contents which are present also in the entire colon
- stomach may or may not be filled w/ milk
How do we diagnose all spp w/ undifferentiated neonatal D+?
- final diagnosis usually needs additional lab tests to ID causative agents due to nonspecific (undifferentiated) clinical signs & gross pathology changes
- MANY OF THE CAUSATIVE AGENTS OF UNDIFFERENTIATED NEONATAL D+ ARE ONLY TRANSIENTLY PRESENT IN THE SUPERFICIAL LAYERS OF THE INTESTINES (ex: SLOUGHED & EXCRETED w/ AFFECTED ENTEROCYTES) & are QUICKLY LOST DURING THE EARLY STAGES OF AUTOLYSIS
- ACCORDINGLY, TO OVERCOME THESE OBSTACLES ONE OR MORE LIVE UNTREATED ANIMALS IN THE EARLY PHASE OF CLINICAL DISEASE & REPRESENTATIVE OF THE HERD PROBLEM, MUST BE EXAMINED & SACRIFICED TO ENSURE HIGH DIAGNOSTIC RATE
- REGULAR NECROPSY PROCEDURE HAS TO BE MODIFIED TO ENSURE THAT INTESTINAL SPECIMENS ARE COLLECTED & FIXED w/in A FEW MINUTES AFTER EUTH, & APPROPRIATE FRESH & UNCONTAMINATED SAMPLES ARE COLLECTED FOR ETIOLOGICAL INVESTIGATION
Who does Enterotoxigenic colibacillosis (ETEC) affect?
- most commonly piglets & calves (& occasionally lambs) during the first weeks of life
- may be fatal
What is the pathogenesis of enterotoxigenic collibacillosis?
- E. coli attach to surface enterocytes by a variety of fimbriae (ex: F4 in piglets & F5 in calves) & produce enterotoxins (Ex: ST, LT) that induce the secretion of Na & Cl into the intestinal lumen
- water is drawn into the intestine by secreted ions
- accordingly, this D+ is called secretory
- absorptive function of the enterocytes persists
What are the clinical signs of enterotoxigenic collibacillosis?
- D+ is voluminous, yellow to white, & watery
- neonates are severely dehydrated (sunken eyes)
- diarrheic feces around perineum
what would we see on necropsy w/ enterotoxigenic collibacillosis?
- small intestines are dilated, flaccid, & filled w/ yellow fluid
- chyle is present in the mesenteric lymphatic vessels similar to animals w/o enteric disease, indicating that absorption proceeds normally unlike the malabsorptive D+
- subgrossly, intestinal villi are present & not affected
How do we diagnose enterotoxigenic collibacillosis?
- preliminary diagnosis may be based on evidence of severe dehydration, D+, & mortality together w/ the presence of chyle in the mesenteric lymphatics & intact villi (no atrophy) observed subgrossly during necropsy
- histo on formalin fixed (not autolysed) small intestines: intestinal mucosa is normal; the only change is bacterial presence on the luminal surface of the enterocytes
- bacterial culture of intestinal contents & PCR demonstration of genes for fimbria & toxins
Who do rotaviruses cause malabsorptive D+ in?
- calves, piglets, lambs, & foals during the first few weeks of life
- each sp of animal has its specific rotavirus & they are not cross-infective
- human rotavirus kills a million children each year in developing countries
what are the clinical signs of rotavirus enteritis?
- neonates are dehydrated, weak, have yellow watery D+
- not fatal D. However, mortality occurs when there is a co-infection w/ other pathogens (ex: ETEC)
what is the pathogenesis of rotavirus enteritis?
- rotavirus targets the most mature villus enterocytes (distal ~1/2 of villus)
- sloughing of injured enterocytes results in moderate villus atrophy
How do we diagnose rotavirus enteritis?
histo (moderate villus atrophy) & IHC on formalin fixed (not autolysed) small intestines
Who do coronaviruses affect?
- cause malabsorptive D+ in calves & piglets during the 1st few wks of life
- in pigs it is called transmissible gastroenteritis (TGE)
What is the pathogenesis of coronavirus enteritis?
- coronavirus targets all enterocytes on the entire villi, therefore villous atrophy is severe resulting in severe diarrhea that may be fatal in neonates
- ‘naked adjacent villi’ w/ exposed basement mbs may adhere & fuse, resulting not only in villous atropy but also in villous fusion, preventing the reformation of normal villi if the animal survives
- this may be the reason that affected surviving animals remain chronic “poor doers”
What are the clinical signs of coronavirus enteritis?
- neonates may be severely dehydrated & weak
- yellow watery D+
- Neonatal morbidity & mortality in susceptible herds approach 100%
How do we diagnose coronavirus enteritis?
- preliminary dx may be based on the presence of villous atrophy observed subgrossly during necropsy
- histo (severe villous atrophy) & IHC on formalin fixed (not autolysed) small intestines
How does coronavirus enteritis affect older pigs?
- in naive pigs older than 3 wks, transmissible gastroenteritis virus (TGE) infection causes transient clinical signs w/ eventual recovery
- sows are susceptible to the virus, and morbidity among the sows is 100%, but the clinical signs are mild & transient (fever, V+, inappetence, & agalactia), & none die
- immunity is solid & transferable through colostrum
What do feline & canine coronaviruses cause?
- mild self-limiting transient D+ in young animals
What is porcine epidemic D+?
- caused by a coronavirus, which is distinguishable from transmissible gastroenteritis of swine (TGE) only by lab tests
- based on clinical presentations, it is difficult to distinguish PED from TGE
- 1st outbreaks in the USA (2013) & Canada (2014) were characterized by explosive epidemics of D+ & V+ in all ages, w/ 90-95% mortality in suckling pigs
- histo revealed sever atrophy of villi in all segments of the small intestines, but testing for rotaviruses & TGE virus were negative
- CONFIRMED + CASE: atrophic enteritis demonstrated by histo & + for PED virus by PCR or virus isolation
What is cryptosporidiosis? who does it infect?
- Cryptosporidium parvum is a cause of malabsorptive D+ in calves & occasionally in lambs & foals
- ubiquitous protozoan pathogen of mammals
- it is a significant cause of municipal water contamination - zoonosis
What is the pathogenesis of cryptosporidiosis?
- cryptosporidia attach to surface epithelial cells of the stomach, small intestine, or colon, & displace & damage the microvilli
- ultimate damage to & loss of enterocytes results in villous atrophy
What are the clinicals signs of cryptosporidiosis?
- watery D+ & dehydration
- usually self-limiting & non-fatal, unless accompanied w/ co-infections w/ other pathogens or immunodeficiency
What would you see on necropsy w/ cryptosporidiosis?
- affected portions of the GI tract contain watery fluid
- cryptosporidia may be observed in intestinal scrapings stained w/ Giemsa or acid fast
How do we diagnose cryptosporidiosis?
- parasitology: demonstration of large numbers of oocytes in feces
- histo: villous atrophy w/ large number of Cryptosporidia in formalin fixed (not autolysed) intestines
